Evidence map›Paper›PMID 34978144›Full record

ArticleChemMedChem2022

Selective Binding of Small Molecules to Vibrio cholerae DsbA Offers a Starting Point for the Design of Novel Antibacterials.

Geqing Wang, Biswaranjan Mohanty, Martin L Williams, Bradley C Doak, Rabeb Dhouib, Makrina Totsika, Róisín M McMahon, Gaurav Sharma, Dan Zheng, Matthew R Bentley and 5 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in ChemMedChem, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 4 papers.

0numbers the graph read from it
0cells of the map it votes in
4citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

4 citing papers in PubMed.

  1. Article
  2. Review
  3. Exploring the inhibitory potential ofFrontiers in molecular biosciences · 2023
    Article
  4. Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

15 authors.

Geqing WangDepartment of Biochemistry and Genetics, La Trobe Institute for Molecular Science, La Trobe University, 3083, Melbourne, Victoria, Australia.
Biswaranjan MohantyMedicinal Chemistry, Monash Institute of Pharmaceutical Sciences, Monash University, 381 Royal Parade, 3052, Parkville, Victoria, Australia.
Martin L WilliamsMedicinal Chemistry, Monash Institute of Pharmaceutical Sciences, Monash University, 381 Royal Parade, 3052, Parkville, Victoria, Australia.
Bradley C DoakMedicinal Chemistry, Monash Institute of Pharmaceutical Sciences, Monash University, 381 Royal Parade, 3052, Parkville, Victoria, Australia.
Rabeb DhouibQueensland University of Technology, Institute of Health and Biomedical Innovation, School of Biomedical Sciences, Brisbane, Queensland, Australia.
Makrina TotsikaQueensland University of Technology, Institute of Health and Biomedical Innovation, School of Biomedical Sciences, Brisbane, Queensland, Australia.
Róisín M McMahonGriffith Institute for Drug Discovery, Griffith University, 4111, Nathan, Queensland, Australia.
Gaurav SharmaMedicinal Chemistry, Monash Institute of Pharmaceutical Sciences, Monash University, 381 Royal Parade, 3052, Parkville, Victoria, Australia.
Dan ZhengMedicinal Chemistry, Monash Institute of Pharmaceutical Sciences, Monash University, 381 Royal Parade, 3052, Parkville, Victoria, Australia.
Matthew R BentleyMedicinal Chemistry, Monash Institute of Pharmaceutical Sciences, Monash University, 381 Royal Parade, 3052, Parkville, Victoria, Australia.
Yanni Ka-Yan ChinInstitute for Molecular Bioscience, The University of Queensland, 4072, St Lucia, Queensland, Australia.
James HorneCentral Science Laboratory, The University of Tasmania, 7005, Sandy Bay, Tasmania, Australia.
David K ChalmersMedicinal Chemistry, Monash Institute of Pharmaceutical Sciences, Monash University, 381 Royal Parade, 3052, Parkville, Victoria, Australia.
Begoña HerasDepartment of Biochemistry and Genetics, La Trobe Institute for Molecular Science, La Trobe University, 3083, Melbourne, Victoria, Australia.
Martin J ScanlonMedicinal Chemistry, Monash Institute of Pharmaceutical Sciences, Monash University, 381 Royal Parade, 3052, Parkville, Victoria, Australia.ORCID 0000-0002-9230-7506

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

DsbA enzymes catalyze oxidative folding of proteins that are secreted into the periplasm of Gram-negative bacteria, and they are indispensable for the virulence of human pathogens such as Vibrio cholerae and Escherichia coli. Therefore, targeting DsbA represents an attractive approach to control bacterial virulence. X-ray crystal structures reveal that DsbA enzymes share a similar fold, however, the hydrophobic groove adjacent to the active site, which is implicated in substrate binding, is shorter and flatter in the structure of V. cholerae DsbA (VcDsbA) compared to E. coli DsbA (EcDsbA). The flat and largely featureless nature of this hydrophobic groove is challenging for the development of small molecule inhibitors. Using fragment-based screening approaches, we have identified a novel small molecule, based on the benzimidazole scaffold, that binds to the hydrophobic groove of oxidized VcDsbA with a K

Indexed as

Escherichia coli ProteinsVibrio choleraeAnti-Bacterial AgentsBacterial ProteinsBenzimidazolesCrystallography, X-RayEscherichia coliHumansLigandsProtein Disulfide-IsomerasesAnti-Bacterial AgentsBacterial ProteinsBenzimidazolesdsbA protein, E coliEscherichia coli ProteinsLigandsProtein Disulfide-Isomerasesantibacterialsbile saltDsbAfragment-based drug discoveryoxidoreductaseVibrio cholerae

Identifiers

PMID34978144
PMCPMC9305425

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Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.